We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Possible Participation of Fas-Mediated Apoptosis in the Mechanism of Atherosclerosis.
- Authors
Fukuo, Keisuke; Nakahashi, Takeshi; Nomura, Shintaro; Hata, Shigeki; Suhara, Toshimitsu; Shimizu, Masumi; Tamatani, Michio; Morimoto, Shigeto; Kitamura, Yukihiko; Ogihara, Toshio
- Abstract
Apoptosis is a programmed cell death that plays a major role during development, homeostasis, and in many diseases. Recent evidence has demonstrated the death of vascular smooth muscle cells (VSMCs) within advanced human atheroma. In the rat balloon-injury model, apoptotic cells were specifically identified in the neointima. The presence of apoptotic cells was demonstrated by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). To clarify the mechanisms that trigger apoptosis in atherosclerotic lesions, we examined whether cytokines released from macrophages can modulate Fas, a death signal, in cultured human VSMCs. Simultaneous treatment with interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) but not with each cytokine alone induced upregulation of Fas in VSMCs. However, coincubation with NG-monomethyl-L-arginine, an inhibitor of nitric oxide (NO) synthesis, inhibited the upregulation of Fas induced by IL-1 and TNF-α. Incubation with sodium nitroprusside, a NO donor, also induced upregulation of Fas in VSMCs. Furthermore, fluorescent nuclear staining with Hoechst 33258 revealed that monoclonal antibody to human Fas significantly enhanced NO-induced apoptotis in VSMCs. These findings suggest that macrophage-derived cytokines can induce upregulation of Fas through a NO-dependent mechanism in VSMCs. Thus, Fas-mediated apoptosis may regulate apoptotic death of VSMCs during atherogenesis. Copyright © 1997 S. Karger AG, Basel
- Publication
Gerontology, 1997, Vol 43, Issue S1, p35
- ISSN
0304-324X
- Publication type
Article
- DOI
10.1159/000213884